Platelet-Derived Growth Factor Promotes the Expression of Peroxisome Proliferator-Activated Receptor γ in Vascular Smooth Muscle Cells by a Phosphatidylinositol 3-Kinase/Akt Signaling Pathway

Vascular diseases such as atherosclerosis are characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs) within the intimal lining. The intimal VSMCs exhibit an increased expression of peroxisome proliferator-activated receptor γ (PPARγ), and the administration of pharmacological PPARγ agonists attenuates vascular lesion formation. The factors that regulate PPARγ expression in the vasculature are poorly defined. Here we report that platelet-derived growth factor (PDGF) upregulates PPARγ by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathway. Using Northern-blotting and Western-blotting analyses, we observed that the levels of PPARγ mRNA and protein were increased by 2- to 3.5-fold in human aortic smooth muscle cells (HASMCs) treated with PDGF (20 ng/mL). This was abolished by preincubation of HASMCs with a PI3-kinase inhibitor (LY294002, 50 μmol/L), and partially inhibited by a MEK1 inhibitor (U0126, 10 μmol/L), but not affected by a p38 kinase inhibitor (SB202190, 10 ...

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